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Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage MPM

Primary Purpose

Malignant Pleural Mesothelioma

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
pleurectomy/decortication
Pemetrexed/Cisplatin
Sponsored by
European Organisation for Research and Treatment of Cancer - EORTC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring pleural mesothelioma, phase II, randomized, surgery, chemotherapy, feasibility

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients aged 18 years or older, with pathologically proven malignant pleural mesothelioma. All histological subtypes are accepted.
  • Stage cT1-3, N0-2, M0 according to UICC TNM classification. FDG-PET-CT scan showing absence of M1, N3, supraclavicular and coeliac node involvement is required. No clinical invasion of mediastinal structures (heart, aorta, spine, esophagus, etc.) and no widespread chest wall invasion (T4) are acceptable. Focal chest wall lesions are acceptable.
  • No prior treatment of any kind for mesothelioma is allowed, especially prophylactic track irradiation after diagnostic procedures.
  • WHO performance status 0-1
  • Fit to receive chemotherapy and undergo a pleurectomy/ decortication with optional removal of hemidiaphragm and pericardium.
  • No history of other malignancy within the last three years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin.
  • No pre-existing peripheral sensory or motor neuropathy > grade I according to CTCAE v4.0
  • No clinically significant pleural effusion that cannot be managed with thoracentesis or pleurodesis (according to institutional practice). If pleurodesis is considered, it should be done before randomization.
  • Adequate organ function Women of child bearing potential must have a negative serum (or urine) pregnancy test within 3 days prior to the start of chemotherapy/surgery. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least three months after the last study treatment.

Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations.

Exclusion Criteria

• Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus).

significant cardiovascular morbidity (assessed by cardiologist) precluding surgery

  • Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery (other than P/D) during the course of study treatment.
  • History of receiving any investigational treatment within 28 days of randomization.
  • History of intolerance to pemetrexed and/or cisplatin.
  • Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.

Sites / Locations

  • UZ Antwerpen
  • UZ Gent
  • The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
  • Erasmus MC Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Immediate pleurectomy/decortication

Delayed pleurectomy/decortication

Arm Description

immediate P/D followed by three cycles of pemetrexed 500mg/m2 IV and cisplatin 75 mg/m2 IV, both drugs given on day 1, every three weeks for non-progressing patients

three cycles of pemetrexed 500mg/m2 IV and cisplatin 75 mg/m2 IV, both drugs given on day 1, every three weeks followed by P/D, for non-progressing patients.

Outcomes

Primary Outcome Measures

Rate of success to complete the full treatment
A patient is considered to be a "treatment success" if he/she meets all of the following criteria: Patient has received the full protocol treatment, defined as 3 cycles of pemetrexed and cisplatin (allowing for the dose adjustments described in section 5.3), preceded/followed by pleurectomy/decortication (P/D) (as described in section 5.3). Patient alive and has no evidence of progression/relapse at week 20 (±2 weeks) after the first day of starting protocol treatment (either chemotherapy or P/D). Patient has no persisting grade 3-4 treatment side-effects (CTCAE V 4.0) at week 20 (±2 weeks) after the first day of starting protocol treatment (either chemotherapy or P/D)

Secondary Outcome Measures

Loco-regional failure free survival
Loco-Regional Failure Free Survival (LRFFS) is defined as the time interval between the date of randomization and the date of relapse in hemithorax or mediastinum or death, whichever comes first
Overall survival
the time interval between the date of randomization and the date of death of any cause
Treatment side-effects
Treatment side-effects will be assessed for all patients and graded per CTCAE category upon occurrence of the event. The investigator will assess whether those events are surgery or/and drug related (no reasonable possibility, reasonable possibility) and this assessment will be recorded in the database for all adverse events. Surgical side effects during the perioperative period will be scored according to the Clavien-Dindo Classification of Surgical Complications as an exploratory approach.

Full Information

First Posted
April 21, 2015
Last Updated
November 4, 2022
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
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1. Study Identification

Unique Protocol Identification Number
NCT02436733
Brief Title
Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage MPM
Official Title
EORTC Randomized Phase II Study of Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage Malignant Pleural Mesothelioma
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 20, 2016 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a multicenter, randomized, 1:1, non-comparative phase II trial. Patients with early stage MPM will be randomized between Arm A: immediate P/D followed by three cycles of chemotherapy (pemetrexed 500mg/m2 and cisplatin 75 mg/m2, both drugs given on day 1, every three weeks) Arm B: three cycles of chemotherapy (same regimen) followed by P/D, for non-progressing patients
Detailed Description
This is an academic led, multicenter, randomized, 1:1, non-comparative phase II trial. Patients with early stage MPM will be randomized between Arm A - immediate surgery: immediate P/D followed by three cycles of chemotherapy (pemetrexed 500mg/m2 and cisplatin 75 mg/m2, both drugs given on day 1, every three weeks) for non-progressing patients Arm B - delayed surgery: three cycles of chemotherapy (same regimen) followed by P/D, for non-progressing patients. A maximum of four weeks (±2 weeks) will be allowed between the baseline tumor assessment and the start of treatment (surgery or chemotherapy). Randomization should be done as soon as possible after baseline tumor assessment. The primary objective of the study is to investigate the feasibility of immediate P/D followed by cisplatin/pemetrexed chemotherapy or deferred P/D after cisplatin/pemetrexed chemotherapy in patients with early stage MPM. The results of this study will allow the LCG to take one of the arms further to a comparative study with either no surgery or EPP as control arm. The choice of the comparator will depend on the result of a parallel ongoing randomized study in the UK, comparing P/D with no surgery

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
pleural mesothelioma, phase II, randomized, surgery, chemotherapy, feasibility

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
64 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Immediate pleurectomy/decortication
Arm Type
Experimental
Arm Description
immediate P/D followed by three cycles of pemetrexed 500mg/m2 IV and cisplatin 75 mg/m2 IV, both drugs given on day 1, every three weeks for non-progressing patients
Arm Title
Delayed pleurectomy/decortication
Arm Type
Active Comparator
Arm Description
three cycles of pemetrexed 500mg/m2 IV and cisplatin 75 mg/m2 IV, both drugs given on day 1, every three weeks followed by P/D, for non-progressing patients.
Intervention Type
Procedure
Intervention Name(s)
pleurectomy/decortication
Other Intervention Name(s)
P/D
Intervention Description
Lung sparing procedures consist of the resection of the pleura without removing the lung
Intervention Type
Drug
Intervention Name(s)
Pemetrexed/Cisplatin
Other Intervention Name(s)
CisPem
Intervention Description
On day 1 of each cycle, pemetrexed 500 mg/m2 should be administered as IV infusion followed by cisplatin 75 mg/m2 as IV.
Primary Outcome Measure Information:
Title
Rate of success to complete the full treatment
Description
A patient is considered to be a "treatment success" if he/she meets all of the following criteria: Patient has received the full protocol treatment, defined as 3 cycles of pemetrexed and cisplatin (allowing for the dose adjustments described in section 5.3), preceded/followed by pleurectomy/decortication (P/D) (as described in section 5.3). Patient alive and has no evidence of progression/relapse at week 20 (±2 weeks) after the first day of starting protocol treatment (either chemotherapy or P/D). Patient has no persisting grade 3-4 treatment side-effects (CTCAE V 4.0) at week 20 (±2 weeks) after the first day of starting protocol treatment (either chemotherapy or P/D)
Time Frame
20weeks
Secondary Outcome Measure Information:
Title
Loco-regional failure free survival
Description
Loco-Regional Failure Free Survival (LRFFS) is defined as the time interval between the date of randomization and the date of relapse in hemithorax or mediastinum or death, whichever comes first
Time Frame
6 months
Title
Overall survival
Description
the time interval between the date of randomization and the date of death of any cause
Time Frame
15 months
Title
Treatment side-effects
Description
Treatment side-effects will be assessed for all patients and graded per CTCAE category upon occurrence of the event. The investigator will assess whether those events are surgery or/and drug related (no reasonable possibility, reasonable possibility) and this assessment will be recorded in the database for all adverse events. Surgical side effects during the perioperative period will be scored according to the Clavien-Dindo Classification of Surgical Complications as an exploratory approach.
Time Frame
36 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients aged 18 years or older, with pathologically proven malignant pleural mesothelioma. All histological subtypes are accepted. Stage cT1-3, N0-2, M0 according to UICC TNM classification. FDG-PET-CT scan showing absence of M1, N3, supraclavicular and coeliac node involvement is required. No clinical invasion of mediastinal structures (heart, aorta, spine, esophagus, etc.) and no widespread chest wall invasion (T4) are acceptable. Focal chest wall lesions are acceptable. No prior treatment of any kind for mesothelioma is allowed, especially prophylactic track irradiation after diagnostic procedures. WHO performance status 0-1 Fit to receive chemotherapy and undergo a pleurectomy/ decortication with optional removal of hemidiaphragm and pericardium. No history of other malignancy within the last three years, except for carcinoma in situ of the cervix or basal cell or spinocellular carcinoma of the skin. No pre-existing peripheral sensory or motor neuropathy > grade I according to CTCAE v4.0 No clinically significant pleural effusion that cannot be managed with thoracentesis or pleurodesis (according to institutional practice). If pleurodesis is considered, it should be done before randomization. Adequate organ function Women of child bearing potential must have a negative serum (or urine) pregnancy test within 3 days prior to the start of chemotherapy/surgery. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least three months after the last study treatment. Before patient registration written informed consent must be given according to ICH/GCP, and national/local regulations. Exclusion Criteria • Current severe, uncontrolled systemic disease (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound healing disorders; ulcers; or bone fractures, known infection with HIV, active hepatitis B and/or hepatitis C virus). significant cardiovascular morbidity (assessed by cardiologist) precluding surgery Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery (other than P/D) during the course of study treatment. History of receiving any investigational treatment within 28 days of randomization. History of intolerance to pemetrexed and/or cisplatin. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jan Van Meerbeeck, Pr.
Organizational Affiliation
UZ Antwerpen, Belgium
Official's Role
Principal Investigator
Facility Information:
Facility Name
UZ Antwerpen
City
Antwerpen
Country
Belgium
Facility Name
UZ Gent
City
Gent
Country
Belgium
Facility Name
The Netherlands Cancer Institute-Antoni Van Leeuwenhoekziekenhuis
City
Amsterdam
Country
Netherlands
Facility Name
Erasmus MC Hospital
City
Rotterdam
Country
Netherlands

12. IPD Sharing Statement

Plan to Share IPD
No

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Pleurectomy/ Decortication (P/D) Preceded or Followed by Chemotherapy in Patients With Early Stage MPM

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